Aydıntuğ-Gürbüz Tuğba, Toprak Fatih, Toprak Selin, Sözer Selçuk
Department of Genetics, Aziz Sancar Research Institute of Experimental Medicine, Iıstanbul University, Çapa Campus, Iıstanbul, Turkey.
Department of Neurosurgery, Haydarpaşa Numune Training and Research Hospital, Istanbul, Turkey.
Basic Clin Neurosci. 2024 May-Jun;15(3):343-354. doi: 10.32598/bcn.2022.3981.1. Epub 2024 May 1.
Ischemic stroke has high morbidity and mortality rates worldwide. Low oxygen (O) levels detected in such conditions create a vulnerable environment for neural stem cells (NSC), altering neuronal function, and leading to neuronal injury or death. There are still no effective treatments for such consequences. This study investigates the molecular and functional effects of growth factors, namely, insulin-like growth factor 1 (IGF-I) and mechano growth factor (MGF), in NSC exposed to low O levels.
An in vitro ischemia model was created by rat hippocampal NSC grown in culture that was exposed to varying oxygen levels, including 0%, 3%, and 20 % for the representation of anoxic, hypoxic, and normoxic conditions, respectively, during 24 h. NSC has investigated , , and gene expressions by real-time reverse transcription polymerase chain reaction. The effects of external administration of growth factors (IGF-I and MGF) on NSC proliferation in such conditions were explored.
Increased and gene expressions were detected in the samples exposed to low O. Anoxia was the highest stimulant for and gene expressions. Meanwhile, HIF1-α that encodes hypoxia-inducible factor-1α revealed downregulation in relative gene expression fold change with IGF-I application in all conditions, whereas application upregulated its change in an anoxic environment. Furthermore, MGF-induced NSC had more proliferationmigration rate in all oxygen conditions. induced significant NSC proliferation in 0% and 20% O.
These findings suggest that IGF-I and MGF expressions were increased to reduce the damage in NSC exposed to low oxygen, and exogenous MGF and IGF-I application increased NSC proliferation at the time of injury. The results might imply the role of exogenous MGF and IGF-I in the treatment of ischemia for relieving the effect of neuronal damage due to their neuroprotective and proliferative effects.
缺血性中风在全球范围内具有较高的发病率和死亡率。在这种情况下检测到的低氧水平为神经干细胞（NSC）创造了一个脆弱的环境，改变神经元功能，并导致神经元损伤或死亡。对于这些后果仍然没有有效的治疗方法。本研究调查了生长因子，即胰岛素样生长因子1（IGF-I）和机械生长因子（MGF），在暴露于低氧水平的神经干细胞中的分子和功能影响。
通过在培养中生长的大鼠海马神经干细胞创建体外缺血模型，在24小时内分别将其暴露于不同的氧水平，包括0%、3%和20%，分别代表缺氧、低氧和常氧条件。通过实时逆转录聚合酶链反应研究神经干细胞的 、 和 基因表达。探讨了在此类条件下外源性施用生长因子（IGF-I和MGF）对神经干细胞增殖的影响。
在暴露于低氧的样本中检测到 和 基因表达增加。缺氧是 和 基因表达的最高刺激因素。同时，编码缺氧诱导因子-1α的HIF1-α在所有条件下应用IGF-I时相对基因表达倍数变化中显示下调，而 在缺氧环境中上调其变化。此外，MGF诱导的神经干细胞在所有氧条件下具有更高的增殖迁移率。 在0%和20%氧条件下诱导神经干细胞显著增殖。
这些发现表明，IGF-I和MGF表达增加以减少暴露于低氧的神经干细胞中的损伤，并且外源性施用MGF和IGF-I在损伤时增加神经干细胞增殖。结果可能暗示外源性MGF和IGF-I在缺血治疗中的作用，因其神经保护和增殖作用而减轻神经元损伤的影响。
